Inflammation is commonly observed in prostatic tissue removed from benign prostatic hyperplasia (BPH) patients, and severity of lower urinary symptoms (LUTS) has been correlated with severity of inflammation. Fibrosis is commonly observed in BPH prostates, but the relationship between prostatic fibrosis and LUTS is unknown. This project will investigate mechanisms that underlie LUTS associated with prostatic inflammation and prostatitis. Two mouse models of prostatic inflammation will be used to pursue these investigations, as well as prostatic tissues, urodynamic data, and medical histories obtained from 250 BPH patients. We will test 3 hypotheses: 1. Acute and chronic prostatic inflammation induce detrussor overactivity and increased voiding frequency; 2. Chronic inflammation causes fibrosis that results in urinary outflow obstruction; and 3. Inflammation accompanies fibrosis in the transition zone of the human prostate, and this observation is accompanied by a history of LUTS. Using the services of the Urologic Biomedical Research Core, and in collaboration with other project leaders, we will investigate mechanistic causes of prostatic inflammation and LUTS. We anticipate that these studies will reveal new mechanistic information that will lead to improved, and individualized, treatment of LUTS in BPH patients.